Marijuana is the most widely abused illegal drug in the United States. Central nervous system responses to the active compound in marijuana include beneficial therapeutic effects, such as analgesia, appetite stimulation, and reduction of nausea and vomiting, while undesired effects include short-term memory and motor impairment, dysphoria, and sedation. The endogenous function of the cannabinoid receptor and the mechanism by which these effects are produced remains ill-defined. The goal of this project is to investigate the role of an uncharacterized cannabinoid receptor interacting protein on the signaling and function of the receptor. The proposed studies will use patch clamp recording of primary neurons to identify the effects of the interacting protein on ion channel modulation and receptor function. A yeast two-hybrid assay will identify the protein-protein interaction domains and confocal microscopy will be used to determine the effect of the novel protein on receptor expression and localization. The results of these studies will increase the knowledge of cannabinoid receptor signaling pathways and function, which is important to facilitate the design of new therapeutic strategies utilizing cannabinoid compounds to select for desired effects, while excluding side-effects. In addition, further insight into the cannabinoid system may lead to a better understanding of marijuana abuse, tolerance and dependence.